Pancreatic cancer is a highly aggressive disease representing the fourth leading cause of cancer-related deaths in the United States. Endoscopic ultrasound (EUS) technology provides a novel, minimally invasive tool to study biomarkers. The proposed project forms the scientific focus of my training grant that capitalizes on my clinical experience in EUS to determine whether a select panel of biomarkers can detect pancreatic neoplasia at an early stage. I propose a validation study of a panel of biomarkers (maspin, cathepsin E, ATDC, CEACAM-1, S100P and CEA-6) for the diagnosis of pancreatic cancer. Preliminary work using, microdissected and surgically obtained specimens has demonstrated that this panel of highly selected biomarkers is expressed and detectable using real-time PCR and successfully differentiates pancreatic cancer from normal pancreas and from chronic pancreatitis, a disease which commonly mimics pancreatic cancer clinically and confounds accurate diagnosis. This proposal will employ a surgical cohort and an endoscopic cohort. In the surgical cohort, I will determine mRNA expression of these biomarkers in tumors as well as in surrounding "normal" pancreas and precancerous lesions (pancreatic intraepithelial neoplasias), using systematic, precisely defined fine needle aspiration (FNA) specimens taken throughout the pancreas in patients undergoing surgical resection for known or suspected pancreatic cancer. In the endoscopic arm, I will determine if this panel of biomarkers alone or in combination is more sensitive or specific for diagnosis than cytology alone and if levels of expression vary based on stage and surgical resectability. Serum, plasma, pancreatic juice and bile will be collected and stored to form a biorepository in anticipation of future validation of serum or pancreatic fluid based biomarkers of pancreatic neoplasia. My career goal is to become an independent translational investigator focused on pancreatic cancer biomarkers. This training grant is proposed to release my time to enable training in molecular diagnostic technologies and experience in the design and conduct of validation trials under the guidance of accomplished mentors. I will attend courses in biomarker development and validation and in the creation of biorepositories. I will recruit patients and personally collect and analyze the specimens obtained. Completing this proposal will allow me to achieve my career goals of becoming an independent translational scientist applying carcinogenesis mechanisms and biomarker discovery technologies in the early diagnosis and risk assessment of pancreatic cancer. Such research would be expected to reduce the mortality associated with this disease.